The present invention provides a method and an apparatus for stimulating and/or modulating growth and differentiation in biological or plant tissue, seeds, plants, and microorganisms. An apparatus of this type includes a pulse generator and a plurality of coils, in which pulsed currents cause fluctuating magnetic fields in a predetermined region holding the material to be stimulated. The fluctuating magnetic fields will induce an electric field in the material.
Pulsed electromagnetic fields (PEMF) have been used widely to treat delayed non-heating fractures, pseudoarthrosis, osteoarthritis, bone fractures and related problems (Bassett, C. A., Mitchell, S. N. and Gaston, S. R. (1981); (Trock et al., 1994). xe2x80x9cTreatment of ununited tibial diaphyseal fractures with pulsing electromagnetic fieldsxe2x80x9d, Journal of Bone and Joint Surgery [American], 63-A, 511-523 and Bassett, C. A. L., Pilla, A. A. and Pawluk, R. J. (1977) xe2x80x9cA non-operative salvage of surgically-resistant pseudarthroses and non-unions by pulsing electromagnetic fields: a preliminary reportxe2x80x9d, Clinical Orthopaedics, 128-143) and have also been suggested for the treatment of nerve growth and wound healing (Sisken, B. F., Kanje, M., Lundborg, G., Herbst, E. and Kurtz, W. (1989), xe2x80x9cStimulation of rat sciatic nerve regeneration with pulsed electromagnetic fieldsxe2x80x9d, Brain Research, 485, 309-316 and Patino, O., Grana, D., Bolgiani, A., Prezzavento, G., Mino, J., Merlo, A. and Benaim, F. (1996), and xe2x80x9cPulsed electromagnetic fields in experimental cutaneous wound healing in ratsxe2x80x9d Joural of Burn Care and Rehabilitation, 17, 528-531). It has been suggested that some of the important effects relating to an enhanced bone growth is the PEMF-induced promotion of angiogenesis, but this issue is not yet resolved (The National Institute of Environmental Health Services (NIEHS): xe2x80x9cAssessment of Health Effects from Exposure to Power-Line Frequency Electric and Magnetic Fieldsxe2x80x9d. (http://www.niehs.nih.gov/emfrapid/home.htm)).
A temporarily varying magnetic flux through an area induces an electric field, E, along the perimeter of the area according to the basic laws of electromagnetism. If the varying magnetic field, B(t), is applied to a material containing free (or mobile) charge carriers, these will be accelerated by the electric field thereby generating eddy currents in the material. The induced electric field or the generated current depends upon the rate of change, dB/dt, of the magnetic field, the electric field or current increasing with increasing rate of change.
The main point in treating biological tissue i.e. bone healing, wound healing, nerve growth, and angiogenesis is the introduction of tissue currents with an intensity and duration that can activate cellular signalling processes and extracellular signals, thus initiating cell proliferation and differentiation and other biological processes.
WO 85/00293 and WO 99/10041 describe the use of conducting coils to stimulate growth and healing in living tissue. The coils are positioned so as to generate a strong field at the region to be treated and a pulsating current signal is supplied for conduction in the coils.
PEMF has been used for activating muscle and neural cells as an alternative method to electrodes see e.g. EP 788 813 or U.S. Pat. No. 5,738,625. PEMF induced by conducting coils has the advantage that no electrodes in direct contact with the skin have to be used. The PEMF used for activating cells must be fast and/or large enough to induce electric potentials large enough to elicit the action potentials of excitable cells. In order to achieve such large electrical potentials, very large currents are used in the coil and the fields from several coils are added. In EP 788 813, the PEMF is used to activate muscle cells to flex a group of pelvic floor muscles in order to treat urinary incontinence. In U.S. Pat. No. 5,738,625, the PEMF is used to activate neural cells in order to investigate or diagnose the nervous system.
The effects of fluctuating magnetic fields in the tissue can be anticipated to be due to the effect of the induced electric field upon charged particles and entities (ions, molecules and macromolecules such as proteins, and inositol phosphates and other signalling compounds, cells and their extracellular signalling compounds such as hormones and other neurotransmitters etc.). Hence, the effects of fluctuating magnetic fields can be anticipated to be due to the extracellular as well as intracellular events caused by the electric fields and currents.
Regarding extracellular effects it can be expected that the on and off rate constants for the associations between neurotransmitters, hormones and their receptors will be affected, to the extent that net positive or negative charges are associated with the process, as well as inducing piezo-electric currents in bone tissue, thus mimicking physiological processes. The intracellular effects that might be the most affected are biochemical reactions that are involved in promoting cell division and differentiation. Amongst cellular signalling processes that have been suggested to be essential for the initiation of cell proliferation is the activation of protein kinase A. This enzyme is activated by cAMP (cyclic adenosine 5xe2x80x2 monophophate) that is synthesised from ATP by a receptor activated adenylyl cyclase. cAMP binds to protein kinase A and forms catalytic subunits, and this signal can be carried to the nucleus. Here it leads to activation of cAMP-inducible genes. Activation of the synthesis of cGMP, by iron containing enzymes such as nitrogen oxide synthetase that in turn activates classes of protein kinase G, are also important candidates. Several studies have implicated that the activation of ornithine decarboxylase, causing synthesis of prutescine and other related compounds, that promotes DNA transcription, also appear to be essential. The mechanism by which signalling processes are initiated appear to be due to a combined effect of proteins with a net charge, that will move in the cell interior (G-proteins, protein kinases, mRNA binding proteins etc.). Those can associate with target proteins and exert a biological effect and changes in the association constants for these processes will affect cellular function. Other ions, such as Ca2+, are highly affected by electrical fields, and will also exert a biological effect by associating with intracellular proteins and ion channels. The essential point is that signalling molecules with net charges or areas with net charges will be affected by the changing magnetic fields and all charged particles will rotate in magnetic fields depending on movements relative to the magnetic field.
One important aspect of promoting growth of osteoblasts, chondroblasts, chondrocytes and their derivatives (bone and cartilage), nerve cells, and other tissues is the induction of growth of small vessels (capillaries) that supply the blood cells, hormones and nutrients for sustaining cell proliferation and differentiation. The small vessels consist of endothelial cells, smooth muscle cells, and other cell types that together will protrude into new areas following the activation of nitric oxide (NO) and growth factors. These cells are also connected to each other both through signalling by chemical substances but also electrically through gap junctions. Both NO, vascular endothelial growth factor (VEGF) and other factors, appear to play an essential role in activating growth and differentiation amongst other things through activation of MAP kinase signalling pathways. However, the intracellular signalling processes play an equally important role in the cellular activation and when considering the effects of PEMF on angiogenesis both extracellular as well intracellular events should be considered.
The induced electric field from a circular coil can be calculated in a plane parallel to the coil, at a given distance from the coil. Due to the cylindrical symmetry, the induced electric field will have a circular symmetry in the plane, and have a maximum at a circle centered at the center axis of the coil with a radius, r, smaller than the radius, R, of the coil. As the distance from the coil to the plane increases, the peak of the maximum flattens out and the radius of the ring shaped maximum varies slightly. Thereby, the maximum of the induced electrical field in a direction away from the coil, form a tubular region centered on the center axis of the coil, and in a plane at a given distance from the coil, the induced electrical field will have a ring shaped maximum with a minimum in the center.
In the apparatuses of the prior art, the region to be treated is centered in the coil thereby experiencing an approximately homogeneous induced electrical field while the ring shaped maximum is positioned in regions encircling the region to be treated. Hence all-over, the field is inhomogeneous.
The biochemical features outlined in the above take place at a large range of electric fields. However, if the induced electrical field gets too high in the region to be treated, it will lead to elicitation of action potentials of excitable cells in the region. Elicitation of cellular action potentials is normally undesirable since it may lead to nuisance for the patient or give rise to undesirable physiological reactions. For example, the effects of the large induced electrical fields in EP 788 813 or U.S. Pat. No. 5,738,625 are a flexing of muscles due to activation of muscle cells or elicitation of nerve impulses due to activation of neural cells. These are undesirable side effects for a person undergoing a continuous treatment.
Therefore, under normal conditions it is not possible simply to increase the current or its rise time in the coils in order to achieve a larger induced electrical field over the region to be treated. The average field can only be increased until the field at the ring shaped maximum reaches the limit for elicitation of the action potentials of cells. Thus the average induced electrical field in the larger central part will not be increased to a very high degree. Hence by increasing the current or its rise time, the field in the region to be treated can only be brought to an average value lying considerably lower than the limit for elicitation of the action potentials of cells. In order to maintain the homogeneous field in the region to be treated, one will pay the price of a lower field and a large stimulation in the surrounding regions, which are not to be treated.
It is therefore an object of the present invention to provide a method and apparatus that stimulates biological tissues that substantially overcomes one or more of the problems due to the limitations and disadvantages of the related art.
The present invention utilizes the realization that stimulation of the biological tissue depends on the magnetic field in a way not previously anticipated. According to investigations performed by the inventors, there is an improved stimulation of the biological tissue in regions lying above or below the perimeter of the coil and not in the regions lying above the center of the coil. Also, the investigations showed that a continuous treatment for longer periods of time (few hours to several days) is often desirable. Hence the efficiency of the biochemical features outlined in the above and giving rise to treatment of biological tissue i.e. bone healing, wound healing, nerve growth and angiogenesis, depends on the induced electrical fields. In order to optimize the effects in the region to be treated, it is desirable to increase the induced electric field in this region and to have a constant average field over the region.
Especially, it has been found that larger B- and/or E-field gradients seem to have a positive effect on the cells, tissue and microorganisms. Such gradients may especially be formed by two coils oppositely polarized and positioned adjacently in relation to the cells. In this manner, especially in the intermediate area of the fields of the coils a larger field gradient is obtained. This effect has not been described hitherto.
The present technique imposes movement of ions and proteins in the tissue from all germinal layers that affects cellular activity in individual cells and in biological tissue as a whole. Important factors are the magnitude of the driving force (through imposing a changing magnetic field strength) with the direction of the magnetic field vectors; the frequency and shape of the pulses and the electrical potential. Those factors determine to which extent a compound possessing a net charge (ions, macromolecules etc.) are affected in a way such that a biological process (proliferation and differentiation) is initiated. The energy level by which the tissue is affected preferably does not cause significant changes in membrane potential and does not evoke action potentials in excitable tissues.
In a first aspect, the invention relates to an apparatus for stimulating living cells, micro organisms, and/or tissue using pulsed electromagnetic fields, the apparatus including a plurality of electrically conducting coils each having center axis, each center axis being directed into the cells, micro organisms, and/or tissue; and a pulse generator operationally connected to each coil for supplying a series of current pulses for conduction in each coil, the series of pulses being adapted to generate a periodically varying magnetic field from each coil for inducing an electrical field, wherein a number of coil pairs, including a first coil and a second coil adjacent to the first coil, exist in each of which, for a given pulse supplied by the pulse generator, the magnetic field at the center of the first coil is directed toward the cells, micro organisms, and/or tissue and the magnetic field at the center of the second coil is directed away from the cells, micro organisms, and/or tissue.
Thus, by providing pairs of coils where the desired E-field gradients are provided, a better influence on the tissue/cells/micro organisms is provided. It should be noted that, naturally, a given coil could be part of a number of pairs in that it will normally have more than one adjacent coil in the apparatus.
In the present context, the center axis of a coil is a symmetry axis normally directed along the central axis of a tubular coil or perpendicularly (positioned centrally) to a plane of a flat coil.
In order to obtain the desired effect over an area exceeding that of merely two coils, it is normally preferred that the number of pairs exceeds half the number of coils in the plurality of coils such as that the number of pairs exceeds 3/4 times the number of coils in the plurality of coils, such as 0.8 times the number of the plurality of coils, such as 0.9 times the number of the plurality of coils, such as being at least substantially equal to the number coils in the plurality of coils. In fact, coil positioning structures exist in which the total number of such pairs exceeds the number of coils in the apparatus by more than a factor of two.
Another manner of defining this manner of obtaining the desired gradients is to provide the apparatus with coils so that, for the given pulse supplied by the pulse generator, in each pair of coils, the first coil is adapted to conduct the current pulse in a clockwise direction and the second coil is adapted to conduct the current pulse in a counter-clockwise direction taken along the center axes of the first and second coils, respectively, in a direction toward the cells, micro organisms and/or tissue.
Again, preferably the first coil of each pair is adapted to conduct the current pulse in a clockwise direction and wherein two, three or more of the nearest neighboring coils of the first cell are adapted to conduct the current pulse in a counter clock-wise direction taken along the center axes of the coils in a direction toward the cells, micro organisms and/or tissue.
Naturally, the number of coils will depend on the actual use of the apparatusxe2x80x94and on the size thereof.
A cross section of each coil, perpendicularly to the center axis, may be at the most 100 cm2, such as at the most 50 cm2, preferably at the most 25 cm2, such as at the most 10 cm2, such as at the most 9 cm2, preferably at the most 8 cm2, such as at the most 7 cm2, preferably at the most 6 cm2, such as at the most 5 cm2, preferably at the most 4 cm2, such as at the most 3 cm2, preferably at the most 2 cm2, such as at the most 1 cm2, preferably at the most 0.5 cm2, such as at the most 0.4 cm2, preferably at the most 0.3 cm2. Smaller coils make it possible to use a large number of coils whereas larger coils are able to provide larger fieldsxe2x80x94such as for use at a larger distance, such as for treating cells, tissue and/or micro organisms inside a container or body.
Normally, the apparatus would include more than 2 coils, and depending on a number of factors, the number of coils may exceed 2, 4, 6, 8, 10, 14, 18, 20, 24 or more.
Naturally, the shape of the coils may be any shape desired. The shape of the coils will be determined on the basis of ease of manufacture, availability and requirements as to the individual positioning.
By using a number of, especially smaller, coils, the induced electric field at a given depth will have many smaller ring shaped maximum regions instead of one large ring shaped maximum regionxe2x80x94together with a number of the desired high gradient areas. Thereby the total induced electric field will be more homogeneous and have a higher average value without eliciting any cellular activation potentials. Also the ratio between low field regions within ring shaped maxima and the total region to be treated is reduced.
The current pulses conducted in the coils preferably include rising and declining phases (two, three or more) resulting in the imposition of an electric field on the charges in the region to be treated. The overall duration of these events may vary depending on the pulse pattern. Thus, the events include increasing and declining magnetic fields that cause the appearance of temporally dependent electric fields on charged particles in particular directions in the tissue. These fields gives rise to the currents in the cells and extracellular environment consisting of moving ions and macromolecules such as proteins and nucleotides as well as amino acid, inositol phosphates and other charged signalling molecules. Thereby, cells are activated in fashion different from events such as i.e. action potentials.
Normally, each coil has a part being at least substantially perpendicular to the center axis of the coil and being adapted to face the cells, micro organisms and/or tissue, the parts of the coils being positioned in one or more planes each including a plurality of coil parts.
The coil may be a flat coil where the part will then be a side surface thereof. Alternatively, the coil may be tubular, where the part would then normally be an end portion thereof.
In order to fit in as many coils in the space as possible, it may be preferred that the parts of the coils within a predetermined area in one of the one or more planes are positioned so as to form so-called closest packing. The closest packing being a manner of packing circular elements optimally.
Also, at least one of the coils may have a part within the predetermined area and has a center to center distance to a nearest neighbor being between 1D-1.5D, where D is the diameter of the one coil.
Different structures may be used in order to provide as many pairs as possible providing the desired gradients. In fact, one preferred structure is the above closest packing which, unfortunately, provides also adjacent coils providing fields in the same direction. Another interesting structure is a honeycomb structure where it is possible for all three coils adjacent to a given coil to have the opposite field than the given coil.
In one embodiment, the plurality of coils is embedded in a flat sheet of flexible material for at least partly surrounding the predetermined cells, microorganisms and/or tissue. Thus, a bendable sheet is provided for surrounding a container, a body part or the like.
In another embodiment, the apparatus includes an even number, larger than two, of coils arranged in sets of two, the coils of each set being adapted to be positioned on at least substantially opposite sides of the cells, micro organisms and/or tissue and having at least substantially coincident center axes. In this manner, the coils may be positioned in one or more flexible sheets or more rigidly fixed e.g. in a tong-like device for at least partly encircling the e.g. container or body part.
Each coil may have a ratio between its inductance and resistance resulting in a pulsed current with a rise time in the range from 0.1 ms to 2 ms and a maximum current corresponding to a maximum magnetic field of 0.05-0.1 Tesla at the center of the coil. This has been found suitable for enhancing angiogenesis in biological tissue.
Also, the pulse generator may be adapted to generate pulses with a frequency in the range from 1 to 300 Hz, such as 10-200 Hz, preferably 20-100 Hz.
Normally, the apparatus will include a power supply for supplying power to the pulse generator. Especially in order to provide a portable apparatus, the power supply may be a battery included within the apparatus and supplying an electric potential of 50 V or less.
Normally, the current pulses fed to the coils will be the same pulses. However, it is possible to actually provide different pulses to different coils, such as pulses having different frequencies. In that situation it is desired that those frequencies are multiples of a basic frequency so that the pulses may be provided at least substantially simultaneously.
It is preferred that the phases of the pulses have a temporal separation in order for the biochemical events to occur, and the two events are therefore normally separated by milliseconds. It has been found suitable to provide a delay of 0.01-10 ms, such as 0.05-5 ms, preferably 0.2-2 ms, such as on the order of 0.5 ms between adjacent pulses for the coils. Also, a time duration of 1-100 ms, such as 2-50 ms, preferably 5-20 ms, such as on the order of 10 ms of the pulses has been found preferred for some applications.
Also, it generally may be desired to provide a treatment over a prolonged period of time, such as a period of time exceeding 15 minutes, such as exceeding xc2xd hour, preferably exceeding 1 hour, such as exceeding 2 hours, such as exceeding 4 hours, preferably exceeding 10 hours, such as exceeding 15 hours, preferably exceeding 1 day, such as exceeding 2 days.
An especially preferred embodiment of the present apparatus is one being adapted to be carried by a person during an operation.
In that and other embodiments, it is desired that the apparatus further includes a fastener for fastening the coils to a body part of a human or animal.
The present invention also relates to two preferred devices that by use of conventional CMOS IC technology create the particular currents in the coils. The devices include timing circuits, made from standard CMOS IC""s with low power consumption. They form a free running asymmetric square wave generator that for example produces an output pulse every 18 ms with a pulse with of for example 3 ms. This pulse is applied to the output stage. The pulse pattern can consist of one or two phases. A CMOS IC, that divides the pulse frequency by 100, drives a control lamp by counting the flashes. This makes it possible to make a simple evaluation of the generator functionality and its frequency. In addition in one device, a magnetometer is incorporated to check the battery and the coils for defects. This circuit includes a little sense coil, an amplifier, a peak rectifier and a comparator that, when beyond threshold, drives the control lamp to light permanently. The comparator threshold is passed when the stimulating coil is functioning correctly when held close to the location of the sense coil.
An alternative to the use of the sensing coil is to have the control lamp flash only when the coil current is within the limits that ensures correct functionality.
In another aspect, the invention relates to the use of the above apparatus. In this case in a second apparatus the coil current is sensed.
Especially, the invention relates to the use of the above apparatus for enhancing tissue growth in a human or an animal, the use including positioning the coils adjacently to the tissue in question and operating the pulse generator.
In this situation, the series of pulses and the coils are preferably selected so that the maximum regions of the induced electrical fields in the predetermined portion are sufficiently small in order not to elicit action potentials in living cells. Normally, a muscle cell or nerve is depolarized to an extent that the membrane potential from xe2x88x9290 mV (muscle) or xe2x88x9270 mV (nerve) reaches its threshold around xe2x88x9255 mV whereby an action potential is elicited. Thus, the present apparatus is able to treat the cells etc. without eliciting excitable tissues.
In one embodiment, the use includes positioning of the coils at the upper or lower jaw of the human or the animal for inducing an enhanced bone growth, such as after extraction of a tooth.
In another embodiment, the use includes positioning the coils at the upper or lower jaw of the human or the animal for promoting in-growth of dental implants.
In yet another embodiment, the use includes attaching the coils to a joint region of the human or the animal for treatment of arthritis or pain, and/or for promoting growth of bone and/or cartilage and/or blood vessels (angiogenesis).
In an alternative embodiment, the use includes attaching two or more coils to a joint region of the human or animal to prevent arthritis or pain or to promote bone growth after a bone fracture.
In another embodiment the apparatus can be used for enhancing the biochemical activity of neural tissue. Three or more coils can be attached to the head and transcranial stimulation conducted without eliciting action potentials but enhancing neural activity resulting in an increased neurosecretion and/or in cell division. This can be applied for i.e. the treatment of depression disorders.
Alternatively, the above apparatus may be used for treating microorganisms, the use including positioning the coils adjacently to the microorganisms in question and operating the pulse generator.
The above apparatus may also, as a matter of fact, be used for treating seeds, plants or plant tissue. This use will include positioning the coils adjacently to the seeds, plants or plant tissue in question and operating the pulse generator.
A third aspect of the invention is a method of treating micro organisms with pulsed electromagnetic fields, the method including providing the above apparatus, directing the center axes of the coils into the micro organisms, and operating the pulse generator.
A fourth aspect of the invention relates to a method for treating cells, micro organisms and/or tissue with pulsating electromagnetic fields, the method including providing a plurality of coils each having a center axis directed into the cells, micro organisms and/or tissue; and providing a series of current pulses to each coil, the series of pulses being adapted to generate a periodically varying magnetic field from each coil for inducing an electrical field, wherein for a given pulse of the series of pulses, and for a number of pairs of the coils, each pair including a first coil and a second, adjacent coil, the magnetic field at the center of the first coil is directed toward the cells, micro organisms, and/or tissue and the magnetic field at the center of the second coil is directed away from the cells, micro organisms, and/or tissue.
Again, it may be preferred that the number of pairs exceeds half the number of coils in the plurality of coils, such as that the number of pairs exceeds 3/4 times the number of coils in the plurality of coils, such as 0.8 times the number of the plurality of coils, such as 0.9 times the number of the plurality of coils, such as being at least substantially equal to the number of coils in the plurality of coils.
Also, it may be preferred to also have the step of providing a part of each coil, the part being at least substantially perpendicular to the center axis of the coil and being adapted to face the cells, micro organisms and/or tissue, in one or more planes each including a plurality of coil parts.
The parts of the coils may be provided within a predetermined area in one of the one or more planes are positioned so as to form the closest packing.
Also, at least one of the coils having a part within the predetermined area may be provided to have a center-to-center distance to a nearest neighbor being between 1D-1.5D, where D is the diameter of the one coil.
In one embodiment, the plurality of coils are embedded in a flat sheet of flexible material and at least partly surrounding the predetermined cells, micro organisms and/or tissue with the flat sheet.
In another embodiment, the providing step includes providing an even number, larger than two, of coils in sets of two, and positioning the coils of each set on at least substantially opposite sides of the cells, micro organisms and/or tissue so as to have at least substantially coincident center axes. Again, these coils may be provided within one or more flexible sheets or e.g. within a more rigid, such as a tong like, structure.
Normally, the method would further include providing a power supply for supplying power to the pulse generator. Especially for a portable apparatus or for safety reasons, the power supply may be a battery included within the apparatus and supplying an electric potential of 50 V or less.
Depending on the actual purpose of the method, the coils and the pulse generator may be desired to provide a series of pulses forming a temporal overlap between the varying magnetic fields from individual coils to form a periodically varying total magnetic field having a frequency in the range from 1 to 1000 Hz.
For the given pulse supplied by the pulse generator, in each pair of coils, the first coil may conduct the current pulse in a clockwise direction and the second coil may conduct the current pulse in a counter-clockwise direction taken along the center axes of the first and second coils, respectively, in a direction toward the cells, micro organisms and/or tissue.
Preferably, the first coil of each pair conducts the current pulse in a clockwise direction and two, three or more of the nearest neighboring coils of the first coil conduct the current pulse in a counter clock-wise direction taken along the center axes of the coils in a direction toward the cells, micro organisms and/or tissue.
Depending on the actual use, each coil may receive, in the series of pulses, a pulsed current with a rise time in the range from 0.1 ms to 2 ms and a maximum current adapted to provide a magnetic field of 0.01 Tesla at the center of the coil, and the pulse generator may generate pulses with a frequency in the range from 1 to 300 Hz.
In a number of applications, it is desired to have a number of coils, such as more than 2 coils, and depending on a number of factors, the number of coils may exceed 2, 4, 6, 8, 10, 14, 18, 20, 24 or more. In the same situation, it may be desired to then choose coils with smaller sizes than those normally used today. Therefore, the step of providing the coils preferably includes providing coils having a cross section, perpendicularly to the center axis, that is at the most 100 cm2, such as at the most 50 cm2, preferably at the most 25 cm2, such as at the most 10 cm2, such as at the most 9 cm2, preferably at the most 8 cm2, such as at the most 7 cm2, preferably at the most 6 cm2, such as at the most 5 cm2, preferably at the most 4 cm2, such as at the most 3 cm2, preferably at the most 2 cm2, such as at the most 1 cm2, preferably at the most 0.5 cm2, such as at the most 0.4 cm2, preferably at the most 0.3 cm2.
One interesting embodiment of the present aspect is the use thereof for treating human cells or tissue. Then, the method may include actually fastening the coils to a body part of a human or an animal. Alternatively, the coils may be provided fixed to e.g. a building, a wall or a bed or as a separate part, such as part of a mattress or a blanket.
Normally, the method includes positioning the coils adjacently to the cells, microorganisms and/or tissue in question and operating the pulse generator.
Preferably, especially when treating cells or tissue of living beings, the series of pulses and the coils are adjusted so as for the maximum regions of the induced electrical fields in the predetermined portion to be sufficiently small in order not to elicit action potentials in living cells.
In one embodiment, the method includes positioning the coils at an upper or lower jaw of a human or an animal for inducing an enhanced bone growth, such as after extraction of a tooth.
In another embodiment, the method includes positioning the coils at an upper or lower jaw of a human or an animal for promoting in-growth of dental implants.
The method may also include attaching the coils to a joint region of a human or an animal for treatment of arthritis or pain, and/or for promoting growth of bone and/or cartilage and/or blood vesselsxe2x80x94so-called angiogenesis.
In a further embodiment, the method may include attaching two or more coils to a joint region of a human or an animal to prevent arthritis or pain or to promote bone growth after a bone fracture.
The method may also be performed for treating microorganisms. Then the method may include positioning the coils adjacently to the microorganisms in question and operating the pulse generator.
Alternatively, the method may be used for treating seeds, plants or plant tissue. Then the method may include positioning the coils adjacently to the seeds, plants or plant tissue in question and operating the pulse generator.
Finally, the invention also relates to a method of treating seeds, plants or plant tissue with pulsed electromagnetic fields, the method including providing an apparatus as described in relation to the first aspect, directing the center axes of the coils into the seeds, plants or plant tissue and operating the pulse generator.
These and other objects of the present invention will become more readily apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating the preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.